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2021年12月12日 时讯速递, 进展交流 暂无评论

Top Stories from #ISICEM21

#ISICEM21: Advances in Resistant Gram-Negative Pneumonia

In an interesting discussion at the 40th ISICEM International Symposium on Intensive Care & Emergency Medicine,  Richard Wunderink, Professor of Medicine, Pulmonary and Critical Care Division of Northwestern University’s Feinberg School of Medicine and Medical Director, Medical ICU, Northwestern Memorial Hospital, Chicago, discussed rising levels of multi-drug resistance and highlighted the need for new treatments in this field.

He talked about the rapid spread of resistance to carbapenems and new treatments that could be effective against carbapenem-resistant pathogens in pneumonia, including Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter species.

Prof Wunderlink discussed new therapeutic options and the recent progress in the development of newer beta-lactam agents and combinations with beta-lactamase inhibitors. He also spoke about meropenem-vaborbactam, the first combination of a carbapenem with a beta-lactamase inhibitor. The TANGO II study has shown high clinical cure rates and reduced nephrotoxicity with this combination. However, meropenem-vaborbactam is only effective against certain classes of carbapenemases.

Prof Wunderlink also spoke about CAZ-AVI - a combination of ceftazidime, a third-generation cephalosporin with avibactam, a non-beta lactic semisynthetic with beta-lactamase inhibitor activity. The REPROVE trial comparing CAZ-AVI to meropenem showed that CAZ-AVI was non-inferior to meropenem in mortality and clinical cure endpoint. Thus, this could be a valuable new tool against CREs and P. Aerigunosa.

Another drug effective against P. Aerigunosa is ceftolozane, a beta-lactam often used in combination with tazobactam, a beta-lactamase inhibitor. The ASPECT-NP trial found that ceftolozane-tazobactam was non-inferior to meropenem treatment in terms of mortality and clinical cure.

Prof Wunderlink discussed yet another new agent - cefiderocol, a siderophore cephalosporin, a broad-spectrum agent. The CREDIBLE-CR trial showed that cefiderocol had similar clinical and microbiological efficacy. Mortality was higher in the cefiderocol group in patients with Acinetobacter infections. The APEKS-NP trial found cefiderocol to be non-inferior in terms of mortality and tolerability to meropenem treatment.

Overall, Prof Wunderlink presented an overview of clinical advances in this field and highlighted new developments that could help improve clinical outcomes.

Source: ISICEM

Image Credit: ISICEM

References:

Bassetti M, Echols R, Matsunaga Y et al. (2021) Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial. Lancet Infect Dis, 21(2):226–240. 

Doi Y (2019) Treatment Options for Carbapenem-resistant Gramnegative Bacterial Infections. Clin Infect Dis, 69(Suppl 7):S565–S575. 

Grundmann H, Glasner C, Albiger B et al. (2017) Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study. Lancet Infect Dis, 17(2):153–163. 

Kollef MH, Nováček M, Kivistik Ü et al. (2019) Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis, 19(12):1299–1311. 

Torres A, Rank D, Melnick D et al.  (2019) Randomized Trial of Ceftazidime-Avibactam vs Meropenem for Treatment of Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (REPROVE): Analyses per US FDA-Specified End Points. Open Forum Infect Dis, 6(4):ofz149. 

Wunderink RG, Giamarellos-Bourboulis EJ, Rahav G et al. (2018) Effect and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial. Infect Dis Ther, 7(4):439–455. 

Wunderink RG, Matsunaga Y, Ariyasu M et al. (2021) Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis, 21(2):213–225.

#ISICEM21: Findings from the REST Trial

Acute hypoxaemic respiratory failure is a leading cause of admission to ICUs and is associated with significant mortality and morbidity. Many patients affected by acute hypoxaemic respiratory failure meet the diagnostic criteria for acute respiratory distress syndrome. An important intervention that has been shown to reduce mortality in patients with acute hypoxaemic respiratory failure and ARDS is ventilation with a lung-protective strategy. However, this can often result in lung hyperinflation and injury. Reducing tidal volumes further may result in respiratory acidosis, which can cause pulmonary hypertension and altered cardiac function.

The REST randomised clinical trial was conducted to determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal would improve outcomes in patients with acute hypoxaemic respiratory failure.

Four hundred and twelve patients from 51 intensive care units in the U.K. were enrolled in the study who received mechanical ventilation for acute hypoxaemic respiratory failure between May 2016 and December 2019. Study participants received lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours or standard care with conventional low tidal volume ventilation. The primary outcome of the study was all-cause mortality 90 days after randomisation. Secondary outcomes included ventilator-free days at day 28 and adverse event rates.

The trial was stopped early because of its futility and feasibility. Findings from the trial show a 41.5% 90-day mortality rate in the lower tidal volume ventilation with extracorporeal carbon dioxide group versus a 39.5% 90-day mortality rate in the standard care group. Study results also show significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group. 31% of patients in the extracorporeal carbon dioxide removal group reported serious adverse events versus 9% in the standard care group.

Overall, these findings show that among patients with acute hypoxaemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation did not reduce 90-day mortality compared with conventional low tidal volume mechanical ventilation.

Source: JAMA

Image Credit: ISICEM 21

References:

McNamee JJ, Gillies MA, Barrett NA, et al. (2021) Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial. JAMA. doi:10.1001/jama.2021.13374

#ISICEM21 - ECMO for COVID-19

At the 40th ISICEM International Symposium on Intensive Care & Emergency Medicine this week, Professor Alain Combes of Sorbonne University, Paris, talked about treating COVID-19 patients with the most severe forms of cardiac and respiratory failure.

Prof Combes talked about his experience during the pandemic and presented his research that compared the first weeks and months of the pandemic last year that showed a mortality rate of 30-35% for patients who received extracorporeal membrane oxygenation (ECMO). He emphasised that outcomes for the patients could have been very different without ECMO.

Prof Combes also discussed findings from an unpublished paper that found that mortality rates reached over 90% in patients denied ECMO. Findings from another study with adult patients infected with SARS-CoV-2 and severe acute respiratory distress syndrome also revealed a link between the use of ECMO and mortality. Study findings show that a shorter time between intubation and ECMO, younger age, and no pre-ECMO renal dysfunction were independently associated with improved 90-day survival.

It is thus important to use precise criteria for ECMO in COVID-19 patients, and these criteria should take into account a centre’s experience into consideration as well. Study findings also show that 90-day survival among ECMO-assisted patients with COVID-19 was associated with the volume of patients treated at different centres. Morality was found to be significantly lower in centres that treated more than 30 VV-ECMO patients a year before the pandemic. Hence, the volume-outcome effect can be strong for ECMO, points out Prof Combes.

At the same time, it is important to mitigate risks from extended periods on ECMO. Before the pandemic, the median time patients remained on ECMO was two weeks, but patients with COVID-19 can be on ECMO for nearly a month, and some are weaned off after over two months of support.

Overall, based on the discussion and findings presented by Prof Combes, ECMO is a vital intervention for COVID-19 patients and can reduce the most severe forms of this infection.

Source: ISICEM 2021

Image Credit: ISICEM 2021

#ISICEM21: COV-BARRIER Study - Baricitinib for COVID-19

A study was conducted to evaluate the efficacy and safety of baricitinib, an oral selective Janus kinase 1/2 inhibitor, in combination with standard of care for the treatment of hospitalised patients with COVID-19.

A total of 1525 participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America and South America. COVID-19 patients receiving standard of care were assigned to receive once-daily 4 mg baricitinib or placebo for up to 14 days. Standard of care included treatment with systemic corticosteroids (such as dexamethasone) and antivirals (including remdesivir).  

The primary endpoint of the study was the proportion of patients who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation or death by day 28. The secondary endpoint included all-cause mortality by day 28. All-cause mortality by day 60 was an exploratory endpoint.

The findings of the study show that 27.8% of the participants who received baricitinib met the primary endpoint compared to 30.5% of the participants receiving placebo. The 28-day all-cause mortality was 8% for the baricitinib group and 13% for the placebo group, corresponding to a 38.2% reduction in mortality. One additional death was prevented per 20 baricitinib-treated participants.

The 60-day all-cause mortality was 10% for the baricitinib group and 15% for the placebo group. Serious adverse events occurred in 15% of participants in the baricitinib group compared to 18% in the placebo group. Serious infections and venous thromboembolic events were similar between both groups.

Overall, these findings show no significant reduction in the frequency of disease progression with the addition of baricitinib to standard of care. However, the addition of baricitinib with standard of care was associated with reduced mortality in hospitalised patients with COVID-19.

Source: The Lancet

Image Credit: iStock

«« #ISICEM21: Advances in Resistant Gram-Negative Pneumonia

#ISICEM21: Awake Prone Positioning for COVID-19 Acute Hypoxaemic Respiratory Failure »»

References:

Marconi VC et al. (2021) Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. The Lancet. doi.org/10.1016/S2213-2600(21)00331-3

#ISICEM21: Awake Prone Positioning for COVID-19 Acute Hypoxaemic Respiratory Failure

Results from the awake prone positioning for COVID-19 acute hypoxaemic respiratory failure meta-trial were presented by Oriol Roca, Critical Care Specialist, Vall d'Hebron University Hospital, Barcelona, Spain, at the 40th ISICEM International Symposium on Intensive Care & Emergency Medicine in Brussels.

Awake prone positioning has been shown to improve oxygenation for patients with COVID-19 in some studies. However, whether it improves patient-centred outcomes remains unknown.

In a collaborative meta-trial of six randomised controlled open-label superiority trials, COVID-19 adult patients who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure were assigned to prone positioning or standard care. Patients from six countries - Canada, France, Ireland, Mexico, U.S. and Spain - were included in the analysis. The primary outcome of the study was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. Secondary outcomes included intubation mortality, use of non-invasive ventilation, length of hospital stay, time to high-flow nasal cannula weaning with treatment success, time to treatment failure, time to intubation, time to death, duration of invasive mechanical ventilation, mortality in invasively mechanically ventilated patients, and predefined safety outcomes and physiological response to awake prone positioning.

A total of 1126 patients were enrolled in the study. 567 patients were assigned to awake prone positioning, while 559 received standard care. 1121 patients were included in the intention-to-treat analysis. Treatment failure occurred in 40% of patients in the awake prone positioning group and in 46% of patients in the standard care group. Awake prone positioning reduced the incidence of treatment failure within 28 days of enrolment in these patients. Incidence of intubation at day 28 was lower in the awake prone positioning group compared to the standard care group. The overall 28-day mortality and the 28-day mortality in invasively mechanically ventilated patients were similar in both groups. The mean duration of invasive mechanical ventilation was also similar. Non-invasive ventilation was used in 17% of patients in the awake prone positioning group and in 20% of patients in the standard care group. Patients in the awake prone positioning group were more likely to be weaned from high-flow nasal cannula up to day 28 compared to the standard care group. SpO2:FiO2, respiratory rate and ROX index were significantly improved during the first awake prone positioning session. The incidence of adverse events was low in both groups.

Findings of this analysis suggest that awake prone positioning of COVID-19 patients with hypoxaemic respiratory failure reduces the incidence of treatment failure and the need for intubation. These results thus support routine awake prone positioning of COVID-19 patients who require support with high-flow nasal cannula.

Source: The Lancet

Image Credit: ISICEM

References:

Ehrmann S et al. (2021) Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. The Lancet. doi.org/10.1016/S2213-2600(21)00356-8

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